Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome: The T-PASS Randomized Noninferiority Trial.

BACKGROUND: Stopping aspirin within 1 month after implantation of a drug-eluting stent for ticagrelor monotherapy has not been exclusively evaluated for patients with acute coronary syndrome. The aim of this study was to investigate whether ticagrelor monotherapy after <1 month of dual antiplatelet therapy (DAPT) is noninferior to 12 months of ticagrelor-based DAPT for adverse cardiovascular and bleeding events in patients with acute coronary syndrome. METHODS: In this randomized, open-label, noninferiority trial, 2850 patients with acute coronary syndrome who underwent drug-eluting stent implantation at 24 centers in South Korea were randomly assigned (1:1) to receive either ticagrelor monotherapy (90 mg twice daily) after <1 month of DAPT (n=1426) or 12 months of ticagrelor-based DAPT (n=1424) between April 24, 2019, and May 31, 2022. The primary end point was the net clinical benefit as a composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding at 1 year after the index procedure in the intention-to-treat population. Key secondary end points were the individual components of the primary end point. RESULTS: Among 2850 patients who were randomized (mean age, 61 years; 40% ST-segment-elevation myocardial infarction), 2823 (99.0%) completed the trial. Aspirin was discontinued at a median of 16 days (interquartile range, 12-25 days) in the group receiving ticagrelor monotherapy after <1 month of DAPT. The primary end point occurred in 40 patients (2.8%) in the group receiving ticagrelor monotherapy after <1-month DAPT, and in 73 patients (5.2%) in the ticagrelor-based 12-month DAPT group (hazard ratio, 0.54 [95% CI, 0.37-0.80]; P<0.001 for noninferiority; P=0.002 for superiority). This finding was consistent in the per-protocol population as a sensitivity analysis. The occurrence of major bleeding was significantly lower in the ticagrelor monotherapy after <1-month DAPT group compared with the 12-month DAPT group (1.2% versus 3.4%; hazard ratio, 0.35 [95% CI, 0.20-0.61]; P<0.001). CONCLUSIONS: This study provides evidence that stopping aspirin within 1 month for ticagrelor monotherapy is both noninferior and superior to 12-month DAPT for the 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily because of a significant reduction in major bleeding, among patients with acute coronary syndrome receiving drug-eluting stent implantation. Low event rates, which may suggest enrollment of relatively non-high-risk patients, should be considered in interpreting the trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797651.

De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials.

BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). FINDINGS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. INTERPRETATION: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. FUNDING: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.

Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea.

BACKGROUND: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year. METHODS: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed. FINDINGS: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups. INTERPRETATION: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions. FUNDING: Abbott Vascular and Cardiovascular Research Center. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

Effect of rosuvastatin versus atorvastatin on new-onset diabetes mellitus in patients treated with high-intensity statin therapy for coronary artery disease: a post-hoc analysis from the LODESTAR randomized clinical trial.

BACKGROUND: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. METHODS: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. RESULTS: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). CONCLUSIONS: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02579499.

Moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome and atherosclerotic cardiovascular disease: A post-hoc analysis of the RACING trial.

AIM: This study evaluated the safety and efficacy of a moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome (MetS) and atherosclerotic cardiovascular disease. MATERIALS AND METHODS: In this post-hoc subgroup analysis of the RACING trial, patients were analysed based on the presence of MetS. MetS was defined as meeting at least three of the five following criteria: (a) elevated waist circumference; (b) elevated triglycerides; (c) reduced high-density lipoprotein cholesterol; (d) elevated blood pressure; and (e) elevated fasting glucose. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. RESULTS: Of the 3780 patients enrolled in the RACING trial, 1703 (45.1%) had MetS at baseline. The primary outcome rate was 10.1% and 10.3% in patients with MetS receiving ezetimibe combination therapy versus high-intensity statin monotherapy (hazard ratio = 0.97; 95% confidence interval = 0.72-1.32; p = .868). Lower rates of intolerance-related drug discontinuation or dose reduction (3.9% vs. 8.0%; p < .001) and lower low-density lipoprotein cholesterol levels (57 vs. 65 mg/dl; p < .001) were observed with ezetimibe combination therapy versus high-intensity statin monotherapy. Furthermore, the rate of new-onset diabetes was 18.5% and 19.1% in each group (p = .822). There were no significant interactions between MetS and therapy regarding study outcomes in the total population. CONCLUSIONS: In patients with MetS and atherosclerotic cardiovascular disease, a moderate-intensity statin with ezetimibe combination therapy had comparable cardiovascular benefits with those of high-intensity statin monotherapy. Meanwhile, ezetimibe combination therapy was associated with lower drug intolerance and low-density lipoprotein cholesterol levels, but there was no apparent between-group difference in new-onset diabetes.

Sex Differences in Outcomes of Ticagrelor Therapy With or Without Aspirin After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: A Post Hoc Secondary Analysis of the TICO Randomized Clinical Trial.

BACKGROUND: We sought to explore the sex differences in clinical outcomes among patients with acute coronary syndrome treated with ticagrelor monotherapy after ticagrelor-based 3-month versus 12-month dual-antiplatelet therapy. METHODS: This was a post hoc analysis of the TICO trial (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome; n=3056)-a randomized controlled trial for patients with acute coronary syndrome treated with drug-eluting stent. The primary outcome was a net adverse clinical event (composite of major bleeding, death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization) 1 year after drug-eluting stent implantation. Secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events. RESULTS: There were 27.3% (n=628) women in the TICO trial; they were older with lower body mass index and higher prevalence of hypertension, diabetes, or chronic kidney disease than men. Compared with men, women had higher risk of net adverse clinical events (hazard ratio [HR], 1.89 [95% CI, 1.34-2.67]), major adverse cardiac and cerebrovascular events (HR, 1.69 [95% CI, 1.07-2.68]), and major bleeding (HR, 2.04 [95% CI, 1.25-3.35]). Among the groups stratified by sex and dual-antiplatelet therapy strategy, the incidences of primary and secondary outcomes were significantly different and the highest in women with ticagrelor-based 12-month dual-antiplatelet therapy (P<0.001). There was no significant heterogeneity in the impact of treatment strategy on the risks of primary and secondary outcomes between both sexes. Ticagrelor monotherapy was associated with a lower risk of the primary outcome in women (HR, 0.47 [95% CI, 0.26-0.85]; P=0.02) and comparable in men (HR, 0.77 [95% CI, 0.52-1.14]; P=0.19) without significant interaction (P for interaction, 0.18). CONCLUSIONS: After percutaneous coronary intervention for acute coronary syndrome, women demonstrated worse clinical outcomes than men. Ticagrelor monotherapy after 3-month dual-antiplatelet therapy was associated with significantly lower risk of net adverse clinical events in women without sex interaction.

Development of Clinically Validated Artificial Intelligence Model for Detecting ST-segment Elevation Myocardial Infarction.

STUDY OBJECTIVE: Although the importance of primary percutaneous coronary intervention has been emphasized for ST-segment elevation myocardial infarction (STEMI), the appropriateness of the cardiac catheterization laboratory activation remains suboptimal. This study aimed to develop a precise artificial intelligence (AI) model for the diagnosis of STEMI and accurate cardiac catheterization laboratory activation. METHODS: We used electrocardiography (ECG) waveform data from a prospective percutaneous coronary intervention registry in Korea in this study. Two independent board-certified cardiologists established a criterion standard (STEMI or Not STEMI) for each ECG based on corresponding coronary angiography data. We developed a deep ensemble model by combining 5 convolutional neural networks. In addition, we performed clinical validation based on a symptom-based ECG data set, comparisons with clinical physicians, and external validation. RESULTS: We used 18,697 ECGs for the model development data set, and 1,745 (9.3%) were STEMI. The AI model achieved an accuracy of 92.1%, sensitivity of 95.4%, and specificity of 91.8 %. The performances of the AI model were well balanced and outstanding in the clinical validation, comparison with clinical physicians, and the external validation. CONCLUSION: The deep ensemble AI model showed a well-balanced and outstanding performance. As visualized with gradient-weighted class activation mapping, the AI model has a reasonable explainability. Further studies with prospective validation regarding clinical benefit in a real-world setting should be warranted.

Treat-to-target or high-intensity statin treatment in older adults with coronary artery disease: a post hoc analysis of the LODESTAR trial.

BACKGROUND: The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). METHODS: In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. RESULTS: Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69). CONCLUSIONS: High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579499.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.

Moderate-intensity statin with ezetimibe vs. high-intensity statin in patients with diabetes and atherosclerotic cardiovascular disease in the RACING trial.

AIMS: This study evaluated the effect of moderate-intensity statin with ezetimibe combination therapy vs. high-intensity statin monotherapy among patients with diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: This was a pre-specified, stratified subgroup analysis of the DM cohort in the RACING trial. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. Among total patients, 1398 (37.0%) had DM at baseline. The incidence of the primary outcome was 10.0% and 11.3% among patients with DM randomized to ezetimibe combination therapy vs. high-intensity statin monotherapy (hazard ratio: 0.89; 95% confidence interval: 0.64-1.22; P = 0.460). Intolerance-related discontinuation or dose reduction of the study drug was observed in 5.2% and 8.7% of patients in each group, respectively (P = 0.014). LDL cholesterol levels <70 mg/dL at 1, 2, and 3 years were observed in 81.0%, 83.1%, and 79.9% of patients in the ezetimibe combination therapy group, and 64.1%, 70.2%, and 66.8% of patients in the high-intensity statin monotherapy group (all P < 0.001). In the total population, no significant interactions were found between DM status and therapy regarding primary outcome, intolerance-related discontinuation or dose reduction, and the proportion of patients with LDL cholesterol levels <70 mg/dL. CONCLUSION: Ezetimibe combination therapy effects observed in the RACING trial population are preserved among patients with DM. This study supports moderate-intensity statin with ezetimibe combination therapy as a suitable alternative to high-intensity statins if the latter cannot be tolerated, or further reduction in LDL cholesterol is required among patients with DM and ASCVD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier:NCT03044665.

Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial.

BACKGROUND: Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed. METHODS: In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete. FINDINGS: Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001). INTERPRETATION: Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction. FUNDING: Hanmi Pharmaceutical.

Potent P2Y12 Inhibitor Monotherapy for Acute Coronary Syndrome.

Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12inhibitor, has been the principal antiplatelet therapy after drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS) and chronic coronary disease. Particularly in patients with ACS, which presents a higher ischemic risk than chronic coronary artery disease, DAPT for up to 12 months is the recommended standard treatment. However, to decrease bleeding events related to the potency of P2Y12inhibitors and a prolonged duration of DAPT, recent studies have suggested P2Y12inhibitor monotherapy after short-term DAPT (1-3 months), which decreased the bleeding risk without an increased ischemic risk. In this article, we discuss the evidence related to the efficacy of a P2Y12inhibitor as single-antiplatelet therapy after short-term DAPT compared with standard DAPT, with a focus on patients with ACS treated with DES.

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial.

Importance: In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease. Objective: To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease. Design, Setting, and Participants: A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022). Interventions: Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg. Main Outcomes and Measures: Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. Results: Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority). Conclusions and Relevance: Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02579499.

Two-year outcomes between ST-elevation and non-ST-elevation myocardial infarction in patients with chronic kidney disease undergoing newer-generation drug-eluting stent implantation.

BACKGROUND: We evaluated the 2-year clinical outcomes of ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) in patients with chronic kidney disease (CKD) who received newer-generation drug-eluting stents (DES). METHODS: Overall, 18,875 acute myocardial infarction patients were divided into two groups: CKD (STEMI, n = 1707; NSTEMI, n = 1648) and non-CKD (STEMI, n = 8660; NSTEMI, n = 6860). The occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (re-MI), any repeat coronary revascularization, and definite or probable stent thrombosis (ST), was evaluated. RESULTS: After multivariable-adjusted analysis, in the CKD group, the MACE (adjusted hazard ratio [aHR]: 1.365, p = 0.004), all-cause death (aHR: 1.503, p = 0.004), noncardiac death (non-CD; aHR: 1.960, p = 0.004), and all-cause death or MI rates (aHR: 1.458, p = 0.002) were significantly higher in the NSTEMI group than in the STEMI group. In the non-CKD group, the non-CD rate (aHR: 1.78, p = 0.006) was also higher in the NSTEMI group. The CD, re-MI, any repeat revascularization, and ST rates were similar between groups. In the CKD group, from 6 months to 2 years after the index procedure, all-cause death, non-CD, and all-cause death or MI rates were significantly higher in the NSTEMI group than in the STEMI group. These results may be related to the higher non-CD rate in the NSTEMI group. CONCLUSIONS: In the era of contemporary newer-generation DES, NSTEMI showed a relatively higher non-CD rate than STEMI in both CKD and non-CKD groups.

Clinical implication of neointimal burden in in-stent restenosis treated with drug-coated balloon.

BACKGROUND: Although drug-coated balloon (DCB) angioplasty is a well-established drug-eluting stent (DES) in-stent restenosis (ISR) strategy, there are minimal data regarding the association of neointimal burden on optical coherence tomography (OCT) before and after DCB and adverse clinical events. This study aimed to investigate the clinical impact of neointimal burden measured with OCT in patients with DES ISR after DCB angioplasty. METHODS: From 2010 through 2013, a total of 122 patients with 122 ISR lesions were treated with DCB, which was preceded and followed by OCT examination. Major adverse cardiac events (MACE, a composite occurrence of cardiovascular cardiac death, nonfatal myocardial infarction [MI], or target lesion revascularization [TLR]) were evaluated. RESULTS: MACE occurred in 27 patients (4 nonfatal MIs and 23 TLRs) during the follow-up (median: 55.3 months, interquartile range 43.1-66.0). The mean lumen area was significantly smaller (3.21 ± 2.42 mm2 vs. 4.80 ± 2.53 mm2 , p = .005) and the mean percentage of neointimal volume derived by OCT was greater (49.3 ± 9.2% vs. 38.3 ± 17.5%, p = .006) in patients with MACE before DCB angioplasty. The pre-procedural mean percentage of neointimal volume (cut-off 50%, area under the receiver operating characteristic [ROC] curve = 0.644, 95% confidence interval [CI] = 0.531-0.758, p = .022) and post-procedural mean percentage of neointimal volume (cut-off 25%, area under ROC curve = 0.659, 95% CI = 0.546-0.773, p = .012) were identified as significant parameters to predict MACE. CONCLUSION: The OCT-derived mean percentages of neointimal volume before and after DCB angioplasty can be important parameters for predicting future MACE in patients with DES ISR.

Safety and usefulness of a novel short track sliding balloon catheter.

OBJECTIVES: To evaluate the safety and technical utility of the short track sliding (STS) balloon catheter. BACKGROUND: An STS balloon catheter is designed to ensure a low profile at the shaft and perform distal anchoring using a single guidewire. However, its clinical practice with the STS balloon catheter has not been reported. METHODS: This prospective multi-center registry enrolled 100 patients with significant coronary artery disease who had undergone percutaneous coronary intervention using an STS balloon catheter at three hospitals in Korea from March 2019 to July 2020. Overall safety was assessed as any occurrences of device-related malfunction during the pre-dilation of the lesions. Its technical success rates of the kissing balloon technique or the distal anchoring technique using a single guidewire were also evaluated. RESULTS: Of the 118 lesions pre-dilated using the STS balloon, no significant complication was observed except for three significant coronary dissections, which were completely covered with stents. There was no incidence of balloon catheter malfunction, such as fracture, entrapment, or perforation. With 13 attempts of kissing ballooning techniques with the STS balloon with a 6F guiding catheter, all cases were successful. The distal anchoring techniques were attempted in 10 cases, the stent was successfully crossed to the target lesion in all 10 cases. CONCLUSIONS: The novel STS balloon catheter can be safely applied in routine coronary intervention with minimal complications. In addition, this catheter could be useful for performing the kissing balloon technique with a small-caliber guiding catheter and distal anchoring technique with a single guidewire.

Ten-Year Clinical Outcomes of Late-Acquired Stent Malapposition After Coronary Stent Implantation.

OBJECTIVE: The goal of this study was to determine the impact of late-acquired stent malapposition (LASM) on long-term clinical outcomes in patients treated with coronary stent implantation. Approach and Results: We investigated major adverse cardiac event during 10 years after 6-month intravascular ultrasound examination using our previous studies database. A total of 732 patients treated with bare-metal stent (54 LASM versus 678 non-LASM) and 529 patients treated with first-generation drug-eluting stent (82 LASM versus 447 non-LASM), who did not have clinical event or censoring at the time of follow-up intravascular ultrasound, were included for the present analysis. major adverse cardiac event was defined as the composite of cardiac death, target vessel-related myocardial infarction, target lesion revascularization and stent thrombosis. Multivariable adjustment and inverse probability weight were performed to consider baseline differences. After multivariable adjustment, LASM was related to a greater risk of major adverse cardiac event (hazard ratio, 1.666 [95% CI, 1.041-2.665]; P=0.0333) and very-late stent thrombosis (hazard ratio, 3.529 [95% CI, 1.153-10.798]; P=0.0271) than non-LASM in patients treated with first-generation drug-eluting stent, but not in those treated with bare-metal stent. Results were consistent after inverse probability weight. Among patients with LASM of first-generation drug-eluting stent, no late stent thrombosis occurred in patients who continued to receive dual antiplatelet therapy. CONCLUSIONS: The relationship between LASM and major adverse cardiac event might depend on the type of implanted stents during the long-term follow-up, highlighting the clinical significance of polymers and drugs in drug-eluting stent system.

Skin Perfusion Pressure Predicts Early Wound Healing After Endovascular Therapy in Chronic Limb Threatening Ischaemia.

OBJECTIVE: Skin perfusion pressure (SPP) has been proposed as a method to predict wound healing in chronic limb threatening ischaemia (CLTI). However, studies regarding the impact of SPP before and after endovascular therapy (EVT) on wound healing are limited. This study sought to evaluate the predictive value of SPP for early wound healing in CLTI treated by EVT. METHODS: Between January 2018 and June 2020, 236 limbs (172 patients) with CLTI that underwent SPP measurement before and after EVT were included. SPP was measured before and 24 - 48 hours after the procedure. Early wound healing was defined as the achievement of complete epithelisation of all wounds without major amputation within three months of EVT. RESULTS: Early wound healing was achieved in 145 (61.4%) limbs after EVT. Baseline SPP (44.1 ± 21.0 mmHg vs. 33.5 ± 21.7 mmHg; p < .001) and post-procedural SPP (61.8 ± 18.5 mmHg vs. 37.4 ± 19.9 mmHg; p < .001) were significantly higher in the wound healing (+) group than in the wound non-healing (-) group. The area under the receiver operating characteristics curve for early wound healing was 0.82 for post-procedural SPP with a cutoff value of 50 mmHg (sensitivity 74.5%, specificity 78.0%). The early wound healing rate was significantly higher with a post-procedural SPP ≥ 50 mmHg compared with a SPP < 50 mmHg (84.4% vs. 35.0%; p < .001). CONCLUSION: Post-procedural SPP with a cutoff value of 50 mmHg was capable of predicting early wound healing after EVT in CLTI.

Impact of PRECISE-DAPT and DAPT Scores on Dual Antiplatelet Therapy Duration After 2nd Generation Drug-Eluting Stent Implantation.

PURPOSE: Determining the optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an important clinical issue. We evaluated the effects of ischemia (by DAPT score) and bleeding (by PRECISE-DAPT score), as well as the impact of DAPT duration, on clinical outcomes. METHODS: From pooled analysis of four randomized clinical trials, 5131 patients undergoing second-generation DES implantation were randomized to short-duration (n = 2575; ≤ 6 months) or standard-duration (n = 2556; ≥ 12 months) DAPT groups. This population was further divided into four subgroups according to PRECISE-DAPT (high bleeding risk ≥ 25) and DAPT (high ischemic risk ≥ 2) scores. RESULTS: Net clinical outcomes (1.3% vs. 1.3%; p = 0.89) and ischemic events (5.0% vs. 4.5%; p = 0.44) did not differ between the two duration groups, although bleeding events were more frequent in patients with standard-duration DAPT (0.4% vs. 0.9%; p = 0.04). Standard-duration DAPT was associated with fewer ischemic events (6.9% vs. 4.0%; p = 0.02) and no increase in bleeding events only among patients at low bleeding risk and high ischemic risk. The other groups show no differences in net clinical outcomes, ischemic events, or bleeding events according to DAPT duration. CONCLUSION: Compared with short-duration DAPT, standard-duration DAPT was associated with similar net clinical outcomes and ischemic events, but more bleeding events at 12 months after second-generation DES implantation. However, standard-duration DAPT reduced ischemic events without increasing bleeding events among patients at low bleeding and high ischemic risk. When determining DAPT duration, considering both ischemic and bleeding risk can help optimize patient benefits. CLINICAL TRIAL REGISTRATION: EXCELLENT (NCT00698607), RESET (NCT01145079), IVUS-XPL (NCT01308281), OPTIMA-C (NCT03056118).